This study has two long-term goals. The first is to determine the physiological role of phospholipid transfer proteins in regulating the structure and function of biological membranes. The second is to determine whether an altered lipid composition, perhaps as regulated by lipid transfer proteins, is a fundamental lesion underlying a number of anomalies of function that are known to be associated with neoplastic cell membranes. In year 1, three Morris hepatomas of various degrees of differentiation were examined. In all three, the levels of nonspecific lipid transfer protein (NS-TP) were reduced to 10% normal. All three tumors showed increased mitochondrial cholesterol content and decreased microsomal phospholipid content which correlated with growth rate, although only minor changes in phospholipid composition were observed. These results do not support previous hypotheses concerning the involvement of NS-TP in lipid transfer from the endoplasmic reticulum to other intracellular membranes or their "rate-limiting" involvement in cholesterol synthesis. In year 2, studies are planned which will elucidate the physiological role of NS-TP. These will involve metabolic studies with cells in culture. Last, the elevated cholesterol-to-phospholipid ratio of the major hepatoma membranes will be examined as a possible contributing factor to the abnormal activities of a number of tumor membrane enzymes.